6-(2-fluorophenylamino)-1H-pyrimidine-2,4-dione | 299442-93-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(2-fluorophenylamino)-1H-pyrimidine-2,4-dione
• 英文别名: 6-(2-fluoroanilino)-1H-pyrimidine-2,4-dione
• CAS: 299442-93-6
• 化学式: C₁₀H₈FN₃O₂
• 分子量: 221.191
• InChiKey: OQBCPLGCBBODJK-UHFFFAOYSA-N

物化性质

• 熔点：
  >360 °C(Solv: water (7732-18-5))
• 密度：
  1.455±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  70.2
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(2-fluorophenylamino)-1H-pyrimidine-2,4-dione 、 2-氟-6-(三氟甲基)苯甲醛 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 以26%的产率得到10-(2-fluorophenyl)-6-(trifluoromethyl)-2H,3H,4H,10H-pyrimido[4,5-b]quinoline-2,4-dione
  参考文献：
  名称：

  5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2

  摘要：

  Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e. g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.09.038
• 作为产物：
  描述：

  6-氯尿嘧啶 、 2-氟苯胺 反应 0.33h， 以84%的产率得到6-(2-fluorophenylamino)-1H-pyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells

  摘要：

  A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.10.011

文献信息

• Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells
  作者：Jennifer M. Wilson、Graham Henderson、Fiona Black、Andrew Sutherland、Robert L. Ludwig、Karen H. Vousden、David J. Robins

  DOI：10.1016/j.bmc.2006.10.011

  日期：2007.1.1

  A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity. (c) 2006 Elsevier Ltd. All rights reserved.
• 5-Deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2
  作者：Michael P. Dickens、Patricia Roxburgh、Andreas Hock、Mokdad Mezna、Barrie Kellam、Karen H. Vousden、Peter M. Fischer

  DOI：10.1016/j.bmc.2013.09.038

  日期：2013.11

  Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure-activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e. g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy. (C) 2013 The Authors. Published by Elsevier Ltd. All rights reserved.